Calcium Phosphate Nanoparticle-Immobilized Macrophage-Derived Extracellular Vesicle Nanohybrid Facilitates Diabetic Bone Regeneration.

IF 26.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Xiaolan Wu,Shanshan Jin,Qibo Wang,Liyuan Chen,Xinjia Cai,Min Yu,Houzuo Guo,He Zhang,Hangbo Liu,Chang Li,Shiying Zhang,Xinmeng Shi,Lifang Feng,Shiqiang Gong,Dan Luo,Cunyu Wang,Yan Liu
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Abstract

Diabetes significantly hinders bone regeneration, and existing tissue engineering therapies struggle to improve the hyperglycemia-induced inflammatory microenvironment, resulting in unbalanced bone remodeling. M2-macrophage-derived extracellular vesicles (M2EVs) possess inherent immunomodulatory properties and promote stem cell differentiation; however, their therapeutic potential in diabetic bone regeneration is significantly limited by poor stability and insufficient osteoinductive capacity. Inspired by biomineralization, a calcium phosphate nanoparticle-immobilized macrophage-derived small extracellular vesicle nanohybrid (M2EV@CaP) is developed by in situ growth of inorganic nanocrystals on M2EV surfaces. In the nanohybrid system, the chemically inert CaP-nanoparticle-reinforced shell provides structural protection for M2EV, inhibiting vesicle aggregation caused by membrane protein denaturation/cross-linking or lipid phase transition through physical barrier. More importantly, M2EV@CaP provides bioavailable calcium/phosphorus ion reservoirs and signaling molecules for bone regeneration and releases responsively under inflammation-induced acidic conditions. In vitro, M2EV@CaP significantly enhances macrophage polarization toward a reparative M2 phenotype, and promotes stem cell osteogenic differentiation under high-glucose inflammatory conditions by activating the Ca2+-Akt signaling axis. In vivo, hydrogel-assisted delivery of M2EV@CaP significantly promotes bone regeneration in diabetic rat calvarial defects through immunomodulation and osteoinduction. This study proposes a nanohybridization strategy based on inorganic nanoparticles reinforcing biostructures, offering a promising extracellular vesicle therapy for complex pathological conditions.
磷酸钙纳米颗粒-固定化巨噬细胞来源的细胞外囊泡纳米复合物促进糖尿病骨再生。
糖尿病严重阻碍骨再生,现有的组织工程疗法难以改善高血糖诱导的炎症微环境,导致骨重塑不平衡。m2 -巨噬细胞来源的细胞外囊泡(m2ev)具有固有的免疫调节特性并促进干细胞分化;然而,它们在糖尿病骨再生中的治疗潜力受到稳定性差和骨诱导能力不足的显著限制。受生物矿化的启发,通过在M2EV表面原位生长无机纳米晶体,开发了磷酸钙纳米颗粒-固定化巨噬细胞来源的小细胞外囊泡纳米杂化物(M2EV@CaP)。在纳米杂化体系中,化学惰性的cap -纳米颗粒增强壳为M2EV提供结构保护,通过物理屏障抑制膜蛋白变性/交联或脂质相变引起的囊泡聚集。更重要的是,M2EV@CaP为骨再生提供了生物可用的钙/磷离子储存库和信号分子,并在炎症诱导的酸性条件下响应性地释放。在体外,M2EV@CaP显著增强巨噬细胞向修复性M2表型的极化,并通过激活Ca2+-Akt信号轴促进高糖炎症条件下干细胞成骨分化。在体内,水凝胶辅助递送M2EV@CaP通过免疫调节和骨诱导,显著促进糖尿病大鼠颅骨缺损的骨再生。本研究提出了一种基于无机纳米颗粒增强生物结构的纳米杂交策略,为复杂病理条件下的细胞外囊泡治疗提供了一种有前途的方法。
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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